This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art.
Gold nanoparticles are widely used as conjugates and contrast agents for a variety of applications in imaging and nanomedicine. They support surface plasmon modes that can be tuned as a function of size, shape, and aspect ratio, with optical resonances ranging from visible to infrared wavelengths. Gold nanoparticles can be made with well-defined shapes: For example, gold nanorods (GNRs) are anisotropic variants of gold nanoparticles with optical resonances defined by their aspect ratio. GNRs have been investigated as contrast agents for optical biomedical imaging modalities such as optical coherence tomography and photoacoustic tomography; they are also capable of producing linear and two-photon excited luminescence, with detection limits at the single-particle level. The large absorption cross sections of GNRs can also generate localized photothermal effects, with application toward the release of molecular cargo and hyperthermic effects on diseased cells and tissues. These attributes have sparked a global effort to develop GNRs into theranostic agents for nanomedicine.
One hurdle in the scalable manufacturing of nanomaterials based on GNRs and other anisotropic gold nanoparticles is the efficient exchange and removal of cationic surfactants such as cetyltrimethylammonium bromide (CTAB), a micellar surfactant commonly used in the batch synthesis of GNRs. CTAB is cationic and moderately cytotoxic (although not insupportably so), much of which can be removed by multiple washes and exchanges with chemisorptive surfactants (e.g., PEGylated thiols or dithiocarbamates), phospholipids, or other surface-active agents. However, CTAB-coated GNR dispersions are frequently destabilized during surfactant exchange, resulting in partial aggregation and low recovery yields. Furthermore, ligand-modified GNRs are often contaminated with residual CTAB, which can induce nonspecific protein adsorption and cell uptake under physiological conditions, or produce surface charge defects in materials applications. It has been shown that CTAB-depleted GNR dispersions can be prepared when using sodium polystyrenesulfonate (Na-PSS) as a mild detergent; nevertheless, the stability of such suspensions remains capricious in subsequent manipulations. There is therefore an unmet need for a practical method for producing CTAB-free GNR dispersions that is universally compatible with surface conjugation protocols.